Effects of dopamine modulation on chronic stress-induced deficits in reward learning

Anhedonia is characteristically preceded by chronic stress, likely involving downstream effects of glucocorticoid alterations on dopamine (DA) function. To elucidate the neural underpinnings of this interaction, we examined whether acute pharmacological modulation of DA alters reward learning after chronic mild stress (CMS). Forty-eight male Wistar rats were exposed to a 21-day CMS regime (n = 48 no stress controls) before completing the probabilistic reward task (PRT), a well-validated cross-species test of reward learning. We first examined whether stress-induced reward dysfunction could be restored by systemic injections of low-dose amisulpride (AMI), which increases DA transmission via D2-like autoreceptor blockade. Then, we investigated region-specific effects through bilateral infusions of quinpirole (QUIN), a D2-like receptor agonist, into either the nucleus accumbens core (NAcc) or medial prefrontal cortex (mPFC). Blunted reward learning in CMS animals was reversed by acute AMI administration, but this treatment did not alter reward learning in the no stress group. Elevated adrenal gland weight, a proxy for stress reactivity, predicted lower reward learning in the untreated CMS group. This effect was extinguished following AMI treatment. These findings might be attributed to significantly higher D2 receptor density in the NAcc of high stress reactive animals. To this end, NAcc QUIN infusions potentiated reward learning relative to mPFC QUIN infusions in CMS rats, but there was no effect in no stress control rats. Collectively, these findings suggest that DA modulation reverses stress-induced reward dysfunction, even among the most stress-reactive animals. The effect might depend on D2-like receptor activation in the mesolimbic system.

Automated summary

Anhedonia, a symptom of depression, may be caused by chronic stress and altered dopamine function. This study found that pharmacological modulation of dopamine can reverse stress-induced reward dysfunction, particularly in animals with high stress reactivity.